Ruthenacycles and Iridacycles as Catalysts for Asymmetric Transfer Hydrogenation and Racemisation

Ruthenacycles, which are easily prepared in a single step by reaction between enantiopure aromatic amines and [Ru(arene)Cl2]2 in the presence of NaOH and KPF6, are very good asymmetric transfer hydrogenation catalysts. A range of aromatic ketones were reduced using isopropanol in good yields with ee’s up to 98%. Iridacycles, which are prepared in similar fashion from [IrCp*Cl2]2 are excellent catalysts for the racemisation of secondary alcohols and chlorohydrins at room temperature. This allowed the development of a new dynamic kinetic resolution of chlorohydrins to the enantiopure epoxides in up to 90% yield and 98% enantiomeric excess (ee) using a mutant of the enzyme Haloalcohol dehalogenase C and an iridacycle as racemisation catalyst.

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Mukaiyama addition of (trimethylsilyl) acetonitrile to dimethyl acetals mediated by trimethylsilyl trifluoromethanesulfonate

(Trimethylsilyl) acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiometric trimethylsilyl trifluoromethanesulfonate (TMSOTf) to yield β-methoxynitriles. The ideal substrates for this reaction are acetals derived from aromatic aldehydes. Elimination to the corresponding α,β-unsaturated nitriles is observed as the major product in the case of electron-rich acetals. A mechanistic hypothesis that includes isomerization of the silylnitrile to a nucleophilic N-silyl ketene imine is presented

長距離走が血液性状におよぼす影響

本実験の目的は長時間走 (21km) が血液性状, 血圧, 体重におよぼす影響について, その走行前後数日間の測定値も考慮して検討を加えることである。本実験に参加した被検者は中京大学体育学部学生, 女子3名, 男子2名の計5名であった。 得られた結果は以下のように要約される。1. 21km走行前後の体重を比較すると, 走行後には主として発汗によると考えられる体重の減少がみられた。女子では1.05～1.10kg, 男子は1.06～2.05kgの体重減少であった。2. 21km走行中著しい血液濃縮がみられた。安静時のHt, Hb, 全血比重, TPの値はそれぞれ44.6±2.4% (5名の平均と標準偏差), 14.7±1.0g/dl, 1.057±0.001, 7.5±0.3g/dlであったが, 21km走行によりそれぞれの値は47.2±1.8%, 15.6±1.0g/dl, 1.061±0.001, 8.4±0.2g/dlまで増加した。3. 血清逸脱酵素 (CPK, LDH, GOT, GPT) は走行中ないし走行後に高値を示す傾向がみられた。 特にCPK活性は走行1日後に最も高い値を示し, 被検者によっては安静時の3倍近くまで増加した。 しかし, 高度な持久的トレーニングを行なっている被検者 (HIM) は走行1日後でもほとんど増加傾向がみられなかった。The purposes of this study were to investigate the effects of 21-km running on blood constituents and to discuss the endurance work capacity from the view point of hemodynamics. The subjects were three female university students and two male ones. Blood constituents, blood pressure and body weight were measured before, during and after 21-km running. The results were summarized as follows : 1) The decrease of body weight due to perspiration was observed in all subjects accompanying running. The difference of body weight between before and after running were 1.05-1.10kg in females and 1.06-2.05kg in males. 2) There was remarkable hemoconcentration during 21-km running. Resting value in Ht, Hb, whole blood specific gravity, TP were 44.5±2.4% (mean±S.D of five subjects), 14.7±1.0g/dl, 1.057±0.001, 7.5±0.3g/dl, respectively but, after running that values increased to 47.2±1.8%, 15.6±1.0g/dl, 1.061±0.001, 8.4±0.2g/dl, respectively. 3) Higher serum enzymes (CPK, LDH, GOT, GPT) activities were observed during and after running compared with before running. Especially, CPK activity showed the highest values after 1 day. The serum enzymes activity observed one day after running in elite distance runner (subject HIM) was, however, almost equal to the value of before running

Stereodivergent Synthesis of Enantioenriched 4-Hydroxy-2- cyclopentenones

Protected 4-hydroxycyclopentenones (4-HCPs) constitute an important class of intermediates in chemical synthesis. A route to this class of compound has been developed. Key steps include Noyori reduction (which establishes the stereochemistry of the product), ring-closing metathesis, and simple functional group conversions to provide a set of substituted 4-HCPs in either enantiomeric form

Structural studies of (rac)-BIPHEN organomagnesiates and intermediates in the halogen-metal exchange of 2-Bromopyridine

Four lithium magnesiate complexes (2−5) containing the dianionic (rac)-BIPHEN ligand have been prepared and characterized using X-ray crystallography and NMR spectroscopy. (THF)3·Li2Mg{(rac)-BIPHEN}nBu2, 2, (THF)3·Li2Mg{(rac)-BIPHEN}(CH2SiMe3)2, 3, and (THF)2·Li2Mg{(rac)-BIPHEN}neoPe2, 4, have been prepared by complexation of the appropriate dialkylmagnesium compound with in situ prepared Li(rac)-BIPHEN in a mixture of hydrocarbon/THF. For all structures, the Mg centers are four-coordinate (and retain the alkyl groups); however, in 2 and 3 the two Li centers have different coordination spheres (one binding to one THF molecule, the other to two). The solid-state structures of 2 and 3 are essentially isostructural with that of 4 except that both Li atoms in this molecule have equivalent coordination spheres. The solution behaviors of these three molecules have been studied by 1H, 13C, and DOSY NMR spectroscopy. During the synthesis of 2, it was discovered that a (rac)-BIPHEN-rich (or n-butyl-free) lithium magnesiate, (THF)4Li2Mg{(rac)-BIPHEN}fo2, 2b, could be isolated. The lithium precursor to 2−5, (THF)4·Li4{(rac)-BIPHEN)}2, 1, has also been isolated. Within the molecular structure of this tetranuclear complex, there are three different Li coordination environments. Finally, 2 has already shown promise as a reagent in a halogen−metal exchange reaction with 2-bromopyridine. The structural chemistry at play in this reaction was probed by X-ray crystallography and NMR spectroscopy. The organometallic intermediate pyridyl-magnesiated 5, (THF)2·Li2Mg{(rac)-BIPHEN}(2-pyridyl)2, was isolated in high yield

Synthesis of Nitrogenated Heterocycles by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)haloimines

Highly optically enriched, protected, nitrogenated heterocycles with different ring sizes have been synthesized by a very efficient methodology consisting of the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines followed by treatment with a base to promote an intramolecular nucleophilic substitution process. N-Protected aziridines, pyrrolidines, piperidines, and azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been obtained in very high yields and diastereomeric ratios up to >99:1. The free heterocycles can be easily obtained by a simple and mild desulfinylation procedure. Both enantiomers of the free heterocycles can be prepared with the same good results by changing the absolute configuration of the sulfur atom of the sulfinyl group.This work was generously supported by the Spanish Ministerio de Ciencia e Innovación (MICINN; grant no. CONSOLIDER INGENIO 2010, CSD2007-00006, CTQ2007-65218 and CTQ2011-24151) and the Generalitat Valenciana (PROMETEO/2009/039 and FEDER). O.P. thanks the Spanish Ministerio de Educación for a predoctoral fellowship (grant no. AP-2008-00989)

Biochemical warfare on the reef : the role of glutathione transferases in consumer tolerance of dietary prostaglandins

© 2010 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 5 (2010): e8537, doi:10.1371/journal.pone.0008537.Despite the profound variation among marine consumers in tolerance for allelochemically-rich foods, few studies have examined the biochemical adaptations underlying diet choice. Here we examine the role of glutathione S-transferases (GSTs) in the detoxification of dietary allelochemicals in the digestive gland of the predatory gastropod Cyphoma gibbosum, a generalist consumer of gorgonian corals. Controlled laboratory feeding experiments were used to investigate the influence of gorgonian diet on Cyphoma GST activity and isoform expression. Gorgonian extracts and semi-purified fractions were also screened to identify inhibitors and possible substrates of Cyphoma GSTs. In addition, we investigated the inhibitory properties of prostaglandins (PGs) structurally similar to antipredatory PGs found in high concentrations in the Caribbean gorgonian Plexaura homomalla. Cyphoma GST subunit composition was invariant and activity was constitutively high regardless of gorgonian diet. Bioassay-guided fractionation of gorgonian extracts revealed that moderately hydrophobic fractions from all eight gorgonian species examined contained putative GST substrates/inhibitors. LC-MS and NMR spectral analysis of the most inhibitory fraction from P. homomalla subsequently identified prostaglandin A2 (PGA2) as the dominant component. A similar screening of commercially available prostaglandins in series A, E, and F revealed that those prostaglandins most abundant in gorgonian tissues (e.g., PGA2) were also the most potent inhibitors. In vivo estimates of PGA2 concentration in digestive gland tissues calculated from snail grazing rates revealed that Cyphoma GSTs would be saturated with respect to PGA2 and operating at or near physiological capacity. The high, constitutive activity of Cyphoma GSTs is likely necessitated by the ubiquitous presence of GST substrates and/or inhibitors in this consumer's gorgonian diet. This generalist's GSTs may operate as ‘all-purpose’ detoxification enzymes, capable of conjugating or sequestering a broad range of lipophilic gorgonian compounds, thereby allowing this predator to exploit a range of chemically-defended prey, resulting in a competitive dietary advantage for this species.Financial support for this work was provided by the Ocean Life Institute Tropical Research Initiative Grant (WHOI) to KEW and MEH; the Robert H. Cole Endowed Ocean Ventures Fund (WHOI) to KEW; the National Undersea Research Center - Program Development Proposal (CMRC-03PRMN0103A) to KEW; Walter A. and Hope Noyes Smith, and a National Science Foundation Graduate Research Fellowship to KEW

Heterogeneously catalyzed lignin depolymerization

Biomass offers a unique resource for the sustainable production of bio-derived chemical and fuels as drop-in replacements for the current fossil fuel products. Lignin represents a major component of lignocellulosic biomass, but is particularly recalcitrant for valorization by existing chemical technologies due to its complex cross-linking polymeric network. Here, we highlight a range of catalytic approaches to lignin depolymerisation for the production of aromatic bio-oil and monomeric oxygenates